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Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
Relationship between the induction of heat shock proteins and the decrease in glucocorticoid receptor during heat
1Department of Pathophysiology, Second Military Medical University, Shanghai, China.
Summary
Heat shock response independently decreases glucocorticoid receptor (GR) activity and induces heat shock proteins (HSPs). Quercetin inhibits HSPs but not GR decrease, showing these are separate events. GR down-regulation by quercetin also impairs cell response.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Glucocorticoid receptor (GR) binding activity decreases during heat shock in HOS-8603 cells.
- Heat shock proteins (HSPs) are induced during heat shock response.
Purpose of the Study:
- To investigate the relationship between heat shock protein induction and GR decrease during heat shock response.
- To determine if quercetin affects GR activity and HSP induction.
- To examine the impact of heat shock on GR functional activity and dexamethasone-induced responses.
Main Methods:
- Utilized HOS-8603 human osteosarcoma cell line.
- Administered heat shock treatment.
- Applied quercetin to inhibit HSP expression.
- Measured GR binding activity and alkaline phosphatase (AKP) activity.
- Assessed dexamethasone (Dex)-induced AKP activity.
Main Results:
- Quercetin inhibited hsp90 alpha and hsp70 mRNA expression but did not prevent GR decrease during heat shock.
- Heat shock alone did not affect AKP activity but blocked dexamethasone-induced AKP activity, indicating decreased GR functional activity.
- Quercetin treatment did not prevent heat shock-induced GR decrease, even when HSP induction was inhibited.
- Quercetin significantly down-regulated GR in a time-dependent manner, paralleling decreased glucocorticoid-mediated responses.
Conclusions:
- Heat shock protein induction and GR decrease during heat shock are independent biological events.
- Heat shock-induced GR alteration is associated with reduced GR functional activity.
- Quercetin down-regulates GR, impacting glucocorticoid-mediated cellular functions.
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